The present application "An Animal Model of Therapeutic Self-Medication for Neuropathic Pain" addresses the broad Challenge Area (15) Translational Science and specific Challenge Topic, 15-DA-112: New Models and Measures in Preclinical Chronic Pain Research. Our long-term goal is to uncover mechanisms for suppressing pathological pain that lack drug abuse liability in humans. The objective of this application is to validate an animal model for assessing therapeutic self-medication of non-psychoactive analgesics. Our novel approach combines assessments of analgesic self-administration behavior with behavioral assessments of antinociception and dependence. Our central hypothesis is that animals will self-medicate with a nonpsychoactive cannabinoid analgesic to attenuate a neuropathic pain state. These studies are innovative because they exploit technological approaches commonly employed to study positive reinforcing effects of abused drugs and apply these methods to a novel context. Here, drug self-administration is used to study negative reinforcing properties of putative analgesics (i.e. ability to attenuate a neuropathic pain state) and dependence liability in the presence and absence of nerve injury. The investigators are well-positioned to conduct the proposed work because we have developed a new preclinical model which demonstrates that animals will self-administer a nonpsychoactive cannabinoid analgesic to attenuate a neuropathic pain state. We, consequently, believe that our self-medication model has broad translational value. We will complete experiments proposed under two Specific Aims: 1) To test the hypothesis that rats will self-administer a nonpsychoactive cannabinoid analgesic to attenuate a neuropathic pain state, 2) To test the hypothesis that a nonpsychoactive cannabinoid analgesic will produce minimal dependence (antagonist-precipitated withdrawal and conditioned place aversion), relative to the opiate analgesic morphine. Completion of this project is expected to validate a novel preclinical model for assessing both analgesic efficacy and drug abuse liability. The development of effective pharmacotherapies for pain with minimal abuse liability is expected to drive down health care costs and alleviate suffering in patients. PUBLIC HEALTH RELEVANCE: Pain is the number one reason Americans access the health care system. Socioeconomic costs of inadequate treatment for pain are estimated at $100 billion annually. The proposed work will develop and validate a rat model for therapeutic self-medication of analgesics. Development of safe and effective drugs that lack abuse potential is necessary to drive down health care costs and improve quality of life in patients.